Emphasis will be placed on two aspects. The first will be the detailed analysis of the initiation process using at first a direct acting carcinogen such as MNU. We are hopeful that we will now begin to pinpoint those changes in DNA and in other macromolecules that might be closely related to the initiation process. Up to now this has not been possible, since the end point that one wishes to correlate with, any base change or other change in a macromolecule is a year to two years off, with many steps in between. It has therefore not been possible to develop a critical way in which one could truly relate any particular change to any step. In addition, we plan to pursue this approach further. What we are actively searching for is a substitute for the 2-AAF in the selection process. We obviously would prefer to have a non-carcinogen that would do this. We now have two leads in this regard. Work by Dr. Lombardi and Shinozuka in Pittsburgh, indicates that perhaps choline deficiency may create the appropriate selection environment. In addition, older work by Van indicates an effect of fructose. We are now pursuing this as well. We are optimistic that we shall be able to find a non-carcinogenic selecting or promoting agent that will enable us to establish clearly a time frame for all of the subsequent steps in carcinogenesis, including the key ones, namely the occurrence of the first neoplastic step. This occurs at about 60 to 70 percent along the time period during the carcinogenic process.